Summary Out-of-hospital cardiac arrest (OHCA) is a major cause of death in the United States and Canada and mechanistically precipitates largely from the epidemic of coronary heart disease. Despite more than five decades since the formal introduction of cardiopulmonary resuscitation (CPR), mortality after OHCA remains high, with an average mortality of approximately 90% across the US. In the last decade, another epidemic, the ever increasing epidemic of opiate drug overdose, has intersected with OHCA, making up a small but significant proportion of OHCA cases by some estimates. Previous studies by our group and others have shown that OD-OHCA cases have higher rates of survival than other etiologies of OHCA and may differ in patient and treatment characteristics from non-OD cases. However, these analyses were generally made in aggregate and did not describe changes in incidence or outcomes over time. Furthermore, previous studies have shown that higher survival rates among OD-OHCA patients persist even though the vast majority of OD-OHCA patients exhibit electrocardiogram (ECG) rhythms at the start of resuscitation that have very poor prognosis. This finding exists against the backdrop of a current multi-year trend in the reduction in proportion of OHCA cases presenting in favorable ECG rhythms, a multifactorial phenomenon that is altering the resuscitation landscape. The goals of the proposed work will be to understand how OD-OHCA has evolved over last decade and how ECG states and state transitions may have contributed to outcomes throughout that period. Our study will be formulated to address 3 specific aims. Our first aim will be to retrospectively describe the temporal evolution of OD-OHCA incidence, outcomes and characteristics as ascertained by the multi-site Resuscitation Outcomes Consortium (ROC) over nearly a decade. Our second aim will be to determine how temporal trends in OD-OHCA relate to concurrent trends in drug overdose (lethal or non-lethal) incidence, as well as contextual socioeconomic and demographic factors. Finally, our third aim will be to provide a detailed characterization of the ECG rhythm states and transitions that occur during OD-OHCA. The findings from the proposed studies will help elucidate how changes in resuscitation practice and the public health burden of drug abuse have altered the occurrence, treatment and outcomes of OD-OHCA over the years, and provide an epidemiological foundation for future public health efforts. Additionally, findings from our ECG aim may help to inform decision- making during resuscitation and provide mechanistic insight into the paradoxical relationship between survival and presenting ECG rhythm among OD-OHCA cases.